| Chapter Ⅰ:Long-term follow-up study of locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapyBackgroundPartial locally advanced rectal cancer(LARC)patients received neoadjuvant chemoradiotherapy(NCRT)can achieve pathological complete response(pCR).Although the prognosis of pCR patients is good,some patients still experience recurrence.Factors affecting the recurrence of pCR patients are still to be studied.MethodsThe clinicopathological data and follow-up information of patients with pathological complete response of rectal cancer after neoadjuvant chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from June 2004 to December 2019 were retrospectively collected.The clinicopathological factors affecting the long-term disease-free survival of patients were analyzed to evaluate the benefits of postoperative chemotherapy.ResultsThe 108 patients included in the study were(56.3±11.6)years old,with male patients accounting for 62.96%(68/108).The median follow-up time of 108 patients was 79.87 months(61.80 months,112.63 months).Twelve patients(11.11%)had local recurrence or distance metastasis.There was recurrence in 9 patients within 5 years.The 5-year diseasefree survival rate was 91.10%.Univariate analysis showed that the maximum diameter of residual tumor/scar(<2.0cm VS ≥2.0cm,HR:8.83,95%CI:1.14～68.46),the distance from the lower edge of the tumor to the anal margin before treatment(≥4.0cm VS<4.0cm,HR:4.67,95%CI:1.26～17.27)were related to disease-free survival time.Multivariate Cox proportional hazards regression analysis showed that the maximum diameter of the residual tumor/scar(HR:8.41,95%CI:1.08～65.22)and the distance from the lower edge of the tumor to the anal margin before treatment(HR:4.54,95%CI:1.23～16.81)were independent risk factors affecting the prognosis.The prognosis of patients was stratified based on independent risk factors.Among patients with the independent risk factors,the 5-year cumulative diseasefree survival rate of patients receiving postoperative standardized chemotherapy was 92.00%,while the 5-year cumulative disease-free survival rate was 82.30%of patients who did not receive or complete standardized chemotherapy.There was a statistically significant difference between two groups(P=0.048).ConclusionsThe maximum diameter of residual tumor/scar and the distance from the lower edge of the tumor to the anal margin before treatment were independent risk factors affecting the prognosis of patients with pathological complete response.Patients with independent risk factors could benefit from standardized postoperative chemotherapy.Chapter Ⅱ:Prognostic value of residual tumor/scar for patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapyBackgroundThe size of residual tumor/scar in locally advanced rectal cancer(LARC)patients after neoadjuvant chemoradiotherapy(NCRT)is considered to represent the original burden of tumor.The prognostic value of residual tumor/scar in the prognosis evaluation of patients after NCRT remains to be further explored.MethodsAfter excluding patients without the residual tumor/scar information or overall survival information from 537 patients with LARC who completed long-term NCRT and underwent total mesorectal excision(TME)from June 2004 to December 2017,a total of 526 patients were included into this research.Univariate and multivariate cox proportional risk regression models were used to analyze independent risk factors that affect the prognosis.A new modified T(MT)staging system was established based on the maximum diameter of residual tumor/scar and the ypT stage.Kaplan Meier survival analysis was used to assess the impact of different clinicopathological indicators on the prognosis.The time-dependent ROC is used to evaluate the prognostic predictive ability of different staging systems.ResultsThe 526 patients included in the study were 55 years old(48 years old,64 years old),with male patients accounting for 66.73%(351/526).The median follow-up time was 77.53 months(64.50 months,94.40 months),with 31.18%(164/526)of patients experiencing recurrence during the follow-up period.The median size of the maximum diameter of the residual tumor/scar is 2.5 cm(range:0.4 cm to 8.0 cm),the median size of the second diameter is 2.0 cm(range:0.2 cm to 6.0 cm),the median size of the third diameter is 0.7 cm(range:0.1 cm to 3.0 cm),and the median size of the area is 5.0 cm2(range:0.2 cm2 to 40.8 cm2).In univariate analysis,factors related to prognosis were the size of the residual tumor/scar,including the maximum diameter(HR:1.417,95%CI:1.241～1.618),the second diameter(HR:1.249,95%CI:1.088～1.434),the third diameter(HR:1.233,95%CI:1.067～1.426),and the tumor area(HR:1.263,95%CI:1.122～1.421),ypT stage(0～2 VS 3～4;HR:3.397,95%CI:2.324～4.967),ypN stage(0 VS 1～2;HR:3.978,95%CI:2.891～5.473),Mandard TRG grade(1～2 VS 3～5;HR:2.253,95%CI:1.561～3.253),the number of negative lymph nodes(NLN)(≥12 VS<12;HR:1.779,95%CI:1.307～2.423).The median value of the timedependent ROC for maximum diameter predicting disease-free survival(DFS)and overall survival(OS)was 0.631 and 0.615,respectively,which were higher than other factors included in the residual tumor/scar.The maximum diameter was considered to be the best representative of the size of residual tumor/scar.The cut-off value for predicting patient prognosis based on X-Tile calculation was 4.0 cm,by which the patients were divided into two groups with significant differences in DFS(P<0.001)and OS(P<0.001).When cut-off values were 2.0 cm and 4.0 cm,patients could be divided into three groups with significant differences in DFS(P<0.001)and OS(P<0.001).In ypT subgroup and ypN subgroup analysis,patients’ DFS and OS could be distinguished based on the maximum diameter.In multivariate cox proportional hazards regression analysis,the maximum diameter(<4cm VS≥4cm,HR:1.880,95%CI:1.340～2.637),ypN stage(0 VS 1&2,HR:1.927,95%CI:1.584～2.344),NLN(≥12 VS<12,HR:1.819,95%CI:1.327～2.494),ypT stage(0～2 VS 3～4,HR:1.938,95%CI:1.268～2.964)and Mandard TRG grade(1～2 VS 3～5,HR:1.636,95%CI:1.104～2.423)were independent risk factors for DFS.The maximum diameter could be used to modify ypT stage into MT stage,and the 5-year DFS of MT 0-4 stage are 100.00%,91.50%,80.10%,65.60%,and 49.00%,respectively.The prognosis difference between MT adjacent stages was more significant than that between ypT adjacent stages,and there were more statistically significant groups between adjacent stages.Time-dependent ROC analysis showed that MT stage(AUC median:0.700,range:0.689～0.715)could more accurately evaluate prognosis than ypT stage(AUC median:0.658,range:0.642～0.671).According to the MT stage,the 5-year restricted mean survival time(RMST)of patients decreased sequentially to 5.00,4.87,4.33,3.95,and 3.40 years,respectively.There were more statistically significant differences between adjacent MT stages of RMST than between ypT stages.In the different ypN stage subgroups,the Kaplan Meier survival curve of MT stage(P<0.001)showed more significant difference in DFS compared than ypT stage(P=0.099).The ypMTNM staging system that includes MT stage has a higher number of statistically significant differences in prognosis compared to the ypTNM staging system for adjacent stage.Time-dependent ROC analysis showed that ypMTNM stage(AUC median:0.797,range:0.778～0.809)could more accurately evaluate prognosis than ypTNM stage(AUC median:0.772,range:0.767～0.775).ConclusionsThe original tumor burden represented by the size of the residual tumor/scar,especially the maximum diameter,has important prognostic value for LARC patients after NCRT.ypT stage could better predict the prognosis of patients after modified by the maximum diameter.Chapter Ⅲ:Study on the recurrence pattern of locally advanced rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapyBackgroundThe purpose of this study was to analyze the recurrence pattern of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy(NCRT)and to modify the follow-up strategy.MethodsThe clinicopathological characteristics and follow-up information of rectal cancer patients with radical surgery after NCRT in the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2004 to December 2017 was retrospectively reviewed.The recurrence pattern including the time and site was explored.ResultsThe 537 patients included in the study were(55.5±11.7)years old,with male patients accounting for 67.22%(361/537).The median follow-up time was 77.90(64.53,95.57)months.30.73%(165/537)patients had distant metastasis or local recurrence,26.82%(144/537)patients had distant metastasis,5.59%(30/537)patients had local recurrence,1.68%(9/537)patients had both distant metastasis and local recurrence.In all the recurrent patients,23.64%(39/165)recurrence was in the first year after surgery,followed by 27.27%(45/165)in the second year,16.97%(28/165)in the third year and 15.76%(26/165)after five years.According to the risk curve drawn by the life table,the highest metastasis risk of patients occurred in the second year after surgery and the metastasis risk peak occurred again after more than five years.The lung was the most common metastatic organ,47.92%(69/144),followed by the liver(18.75%,27/144).The ratio of the recurrent patients in each ypTNM stage was:ypTNM 0 stage,9.52%(8/84);ypTNM 1 stage,12.00%(12/100);ypTNM 2 stage,26.45%(41/155);ypTNM 3 stage,52.53%(104/198),respectively,and the proportion of each ypTNM of the recurrent patients was 4.85%(8/165),7.27%(12/165),24.85%(41/165),63.03%(104/165),respectively.The proportion of recurrent patients in TRG 1～2 and TRG 3～5 patients were 19.19%(38/198)and 37.46%(127/339),respectively,accounting for 23.03%(38/165)and 76.97%(127/165)of all recurrent patients.ConclusionsThe recurrence pattern of patients after NCRT mainly was distant metastasis.The lung was the most common metastatic organ.The risk of distant metastasis and local recurrence was high in the first three years after surgery,and there was still high risk on recurrence after five years.For patients with ypTNM 2,3 stage and poor treatment response,the postoperative adjuvant chemotherapy and long-term follow-up should be intensively strengthened. |
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